Chapter 30 Microbial Interactions (미생물의 상호작용) 1 공생 (Symbiosis) • 상리공생 (mutualism) – 서로 이익 • 협동관계 (cooperation) – 서로 분리되는 죽 음 • 편리공생 (commensalism) – 한쪽만 이익 • 포식작용 (predation) • 기생 (parasitism) – 한쪽은 이익, 한쪽은 해 • 편해작용 (amensalism) ‐ 한쪽만 해 • 경쟁 (competition) 2 노토바이오틱 동물 • 무균상태 (germ‐free) • 노토바이오틱 (gnotobiotic) – 모든 미생물을 알고 있는 상태 – 미생물학적 조사가 가능한 무균상태 3 Normal Microbiota of the Human Body • Normal microbiota (고유미생물상), microflora (미생물총), or normal flora (정상 세균총) – Microbes regularly found at an anatomical site • Relationship begins at birth • Varies with environment and food source 4 Reasons to Study Normal Human Microbiota • To gain insight into possible infections resulting from injury • To understand causes and consequences of overgrowth of microbes normally absent from a body site • To increase awareness of role played by indigenous microbe in stimulating immune response 5 기회감염 (opportunistic infection) • 기회감염 미생물 (opportunistic microorganism) • 기회감염 병원체 (opportunistic pathogen) • 약화된 숙주 (compromised host) 6 Chapter 31 감염과 병원성 (Infection and Pathogenicity) Host, parasites, and infection • Host (숙주) – Larger organism that supports the survival and growth of a smaller organism • Parasites (기생생물) – Organisms that live on or within a host organism – Metabolically dependent on the host – Any organism that cause disease • Infection (감염) – A parasite growing and multiplying within or on a host Pathogen and pathogenicity • Pathogen (병원균) – Any parasitic organism that causes infectious disease – Primary pathogen (1차 병원체) • Causes disease by direct interaction with healthy host – Opportunistic pathogen (기회감염 병원체) • Causes disease only when it has gained access to other tissue sites or host is immunocompromised • Pathogenicity (병원성) – Ability of parasite to cause disease Active versus latent infection • Active infection (활성 감염) – Transmission of the organism occurs – Symptoms are present within the host • Latent infection (잠복 감염) – No transmission of the organism occurs – No symptoms are present within the host – Herpesvirus infection, tuberculosis and leprosy Factors Impacting Outcome of Host‐ Parasite Relationships • Number of organisms present (개체수) • The degree of virulence of pathogen (독성인자) • Host’s defenses or degree of resistance (숙주 저 항성) The Infectious Disease Process • Infectious disease (감염성 질병) – Infection with viruses, bacteria, fungi, protozoa (원생동물), and helminths (기생충) • Signs (징조) – Objective changes in body that can be directly observed • Symptoms (증상) – Subjective changes experienced by patient • Disease syndrome – Set of characteristic signs and symptoms Course of Infectious Disease • Incubation period (잠복기) – Period after pathogen entry but before signs and symptoms appear • Prodromal stage (전구기) – Onset of signs and symptoms – Not clear enough for diagnosis • Period of illness (질병기) – Disease is most severe and has characteristic signs and symptoms • Convalescent period (회복기) – Signs and symptoms begin to disappear The Source or Reservoir • Source (감염원) – Location from which pathogen is transmitted to host • Period of infectivity (감염기간) – Time during which source is infectious or is disseminating the organism • Reservoir (보유체) – Site or natural environmental location in which pathogen is normally found • Carrier (보균자) – Infected hosts who are potential sources of infection for others Pathogen Transmission (병원체의 전파) • Transmission alone not enough for infection to occur • Tropism (친화성) ‐ pathogen must make contact with appropriate host tissue – Determined by specific cell surface receptors – Hepatitis viruses only infect liver 인수공통전염병 • 인수공통전염병 (zoonosis) • 동물에서 사람에게 감염 • 매개자 (vector) 16 Pathogen Transmission • Four main modes of transmission – Airborne (공기매개) – Contact (접촉성) – Vehicle (운반체) – Vector borne (매개자) Growth of Pathogen • Extracellular pathogens (세포외 병원체) – Grow outside cells in blood, tissue fluids • Intracellular pathogens (세포내 병원체) – Grow and multiply within cells – Facultative (조건부) intracellular pathogens • Grow within or outside cells – Obligate (절대) intracellular pathogens • Only grow when inside cells Host Susceptibility (감수성) • Two main factors – Defense mechanisms of host (숙주 방어기전) – Pathogenicity of pathogen (병원성) • Nutrition, genetic predisposition, and stress also play a role in host susceptibility to infection Exiting the Host (숙주 탈출) • Must occur if microbe is to be perpetuated • Active escape (능동적 탈출) – Movement of pathogen to portal of exit • Passive escape (수동적 탈출) – Excretion in feces, urine, droplets, blood, saliva, or desquamated (벗겨지는) cells Virulence (독성) • Degree or intensity of pathogenicity • Virulence factors (독성인자) – Determine the degree to which the pathogen causes damage, invasion, infectivity • Determined by characteristics of the pathogen – Adherence (부착) and colonization (집락화) – Invasion (침입) Adherence and Colonization • Adherence (부착) – Mediated by special molecules or structures called adhesins • Colonization (집락화) – Establishment of a site of microbial reproduction on or within host Invasion (침입) • Infectivity (감염성) – Ability of the organism to establish a discrete, focal point of infection • Invasiveness (침입성) – Ability of organism to spread to adjacent or other tissues • Penetration of host’s mucous membranes ( 점막) or epithelium (상피) can be active or passive Active Invasion (능동 침입) • Lytic substances (용해성 물질) – Attack the extracellular matrix and basement membranes of integuments (외피) and intestinal linings – Degrade carbohydrate‐protein complexes between cells – Disrupt host cell surface Passive Invasion (수동 침입) • Penetration through skin lesions, insect bites, wounds • Once below mucous membrane (점막), bacterium can spread to deeper tissues • Involves production of specific products and/or enzymes that promote spreading Invasion (침입) • Once in circulatory system, microbes have access to all organs and systems – Bacteremia (균혈증) – presence of viable bacteria in the blood – Viremia (바이러스혈증) ‐ spread of viruses in the blood and hence gain access to the rest of body – Septicemia or sepsis (패혈증) – bacteria, other pathogens, or their toxins in the blood Resisting Host Defenses • Most microbes eliminated before they can cause disease due to immune system • Successful pathogen evades immune system • Numerous mechanisms for both viral and bacterial pathogens Mechanisms Resisting Host Defenses 1 • Infection of immune system cells, diminishing their function • Fuse with adjacent cells to prevent exposure to antimicrobial proteins in host • Capsules and specialized surface proteins prevent phagocytosis • Production of decoy (유인) proteins to bind available neutralizing antibodies Mechanisms Resisting Host Defenses 2 • Mutations (돌연변이) change antigenic sites or alter expression of antigens through downregulation of phase variation • Produce substances that resemble host tissue • Produce proteases that degrade host proteins • Special proteins that interfere with host defenses Toxigenicity • Toxigenicity (독소생성력) – Ability to produce toxins • Intoxications (중독) – Diseases that result from entry of a specific preformed toxin into host • Toxin (독소) – Specific substance that damages host • Toxemia (중독증) – Condition caused by toxins in the blood of host Exotoxins (외독소) • Soluble, heat‐labile (열에 불안정한) proteins • Usually released into the surroundings as bacterial pathogen grows • Most exotoxin producers are gram‐positive • Often travel from site of infection to other tissues or cells where they exert their effects Exotoxins (외독소) • Usually synthesized by specific bacteria that have toxin genes in their plasmids or prophage DNA • Among the most lethal substances known are highly immunogenic (면역반응유도) • Can stimulate production of neutralizing antibodies (중화항체) or antitoxins (항독소) • Can be chemically inactivated to form immunogenic toxoids (변성독소) to be used as vaccine Types of Exotoxins (외독소의 종류) • • • • AB exotoxins Specific host site exotoxins Membrane‐disrupting exotoxins Superantigens AB Exotoxins • Composed of two subunits – A subunit – responsible for toxic effect – B subunit – binds to specific target cell • Mechanisms of action – Protein synthesis inhibition (ADP ribosylation of EF‐2 factor) – Ribonuclease activity – Signal transduction interference – Blocking neurotransmitters Specific Host Site Exotoxins • Can be AB toxins • Neurotoxins (신경독소) – Target nerve tissue – Botulinum and pertussis toxins • Enterotoxins (장독소) – Target intestinal mucosa – Cholera and E.coli toxins • Cytotoxins (세포독소) – Target general tissues – Diphtheria and Shiga toxins Membrane‐Disrupting Exotoxins (막파괴 외독소) • Do not have separable A and B subunits • Pore‐forming exotoxins (통로형성 외독소) • Phospholipases (인지질 분해효소) Pore‐Forming Exotoxins • Leukocidins (백혈구 독소) – Kill phagocytic leukocytes • Hemolysins (용혈소) – Kill erythrocytes, leukocytes, and many other cells Phospholipase Enzymes • A second subtype of membrane‐disrupting toxins • Remove charged head group from lipid part of phospholipids in host‐cell plasma membranes • Membrane destabilizes, cell lyses, and dies • Clostridium perfringens, 가스괴저균 Superantigens • Stimulate ~30% of T cells of the immune system • Causes the T cells to overexpress and release cytokines • Results in failure of multiple host organs allowing time for the microbe to disseminate • Staphylococcal enterotoxin B (포도상구균 장독소 B, SEB) Endotoxins (내독소) • Bacterial cell wall lipopolysaccharide (LPS, 지질다당체) in gram‐negative cell wall can be toxic to specific hosts • Bound to bacterium and released when organism lyses and some is also released during multiplication • Toxic component is the lipid portion, lipid A Lipopolysaccharide (지질다당체, LPS) Endotoxins (내독소) • • • • • Heat‐stable (열에 안정) Toxic (nanogram amounts) Weakly immunogenic Generally similar, despite source Cause general system effects – Fever, weakness, diarrhea, inflammation, intestinal hemorrhage, and fibrinolysis (섬유소 용해), the enzymatic breakdown of fibrin, the major protein component of blood clots Endotoxins (내독소) • Bring about these effects indirectly • Endotoxin interacts with host molecules and cells, activating host systems • Activation of coagulation (응고), complement (보체), fibrinolytic (섬유소용 해), and kininogen system 43 Endotoxins (내독소) • Interaction with macrophages release of endogenous pyrogen (내인성 발열인자) such as IL‐1 (interleukin‐1), which induces fever) • Binding to LPS‐binding protein release of cytokines including tumor necrosis factor (TNF) and others lead to septic shock (패혈 성 쇼크) 44 외독소와 내독소의특징 Mycotoxins (진균독소) • Secondary metabolites of fungi – Common contaminants of food crops – Aspergillus flavus and A. parasiticus produce carcinogenic aflatoxin – Stachybotrys produce tissue‐damaging satratoxins – Claviceps purpurea (ergot) produce hallucinogen lysergic acid Measuring Virulence • Lethal dose 50 (LD50) – Dose that kills 50% of experimental animals within a specified period • Cytopathology – cellular changes • Examining virulence factors and their release
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